Background: Anastomosis of gastrointestinal tract more commonly used in most of abdominal operations including esophagus, stomach, small intestine, large intestine, and biliary system. However single layer versus double layer anastomotic technique is still a matter of discussion as regard safety and efficacy. Objective: To study efficacy and safety of single layer intestinal anastomosis against double layer anastomosis as regard leakage, cost effectiveness, and the time of the procedure. Patients and methods: This prospective randomized study included 40 patients requiring small intestinal resection and anastomosis at Al- Hussein University Hospital and Damanhur Medical National Institute (Al-Behira) during the period between May 2019 and October 2020. The cases of this study were subjected to full history taking, full clinical examination, along with routine laboratory and radiological investigations. The cases of this study were divided into two equal groups randomly; Group A was subjected to one-layer anastomosis, and group B underwent double layered anastomosis. All cases were subjected to the standard post-operative care. Oral intake and hospital stay were recorded. In addition, post-operative complications including leakage, ileus, and mortality were recorded. Results: Mean time of operation in the single layer intestinal anastomosis was statistically significantly shorter as compared with double layered intestinal anastomosis (28.29 ± 8.15 minutes and 35.19 ± 9.96 minutes) respectively. The early postoperative findings and late postoperative complications were comparable in both groups with no statistically significant difference. Conclusion: Single layer intestinal anastomosis was less time consuming, less utilization of packing material, in addition to equal efficacy and safety as compared with double layer intestinal anastomosis.